Natural killeer (NK) cells are leukocytes that can kill tumor cells without having had prior contact with them. Natural killer cells are considered by many investigators to be a first line of defense against tumor cells. Environmental factors that can either enhance or inhibit the tumoricidal activity of NK cells would obviously play a very important role in the survival, growth, and metastases of tumor cells. We recently observed that the acquisition of an intestinal flora enhances the tumoricidal activity of splenic NK cells harvested from athymic and euthymic BALB/c mice. For many years, epidemiological data has pointed to a connection between the intestinal flora, diet, and cancer of the breast and colon. Mucosal surfaces of the alimentary and genito-urinary tract are in constant contact with myriad microorganisms. Many investigators have looked for mutagens, carcinogens, or cocarcinogens that would be produced by intestinal microbes in people at high risk for developing breast or colon cancer. Mutagens and cocarcinogens, however, appear to be commonplace in the intestinal con of both high risk and low risk groups. Our study opens up a new avenue of research to explain the association between diet, intestinal flora, and cancer by exploring the effect of intestinal bacteria on the tumoricidal activity of NK cells in the spleen and especially the intestinal lamina propria of mucosal surfaces which are in constant contact with viable microbes. The mucosal microflora, depending on it's composition, can exert either an enhancing or a suppressive effect on the tumoricidal activity of NK cells in the spleen and the lamina propria. It is worth pointing out that prior to our studies several reports stated that the microbial flora did not have an effect on NK cell activity. Our work shows that the intestinal flora can have a pronounced and long-terrm affect on the tumoricidal activity of NK cells. We want to expand our original observation and carry out studies to learn more about the this important association between intestinal flora and the tumoricidal activity of NK cells. Our results will be very pertinent to the etiology of cancers that develop in or on any mucosal tissue that is in constant or intermittent contact with a microbial flora.